Hepatitis C virus transmission between eight high-income countries among men who have sex with men: a whole-genome analysis
Authors: Jelle Koopsen, Gail Matthews, Juergen Rockstroh, Tanya L Applegate, Sanjay Bhagani, Andri Rauch, Jason Grebely, Rachel Sacks-Davis, Patrick Ingiliz, Christoph Boesecke, Sjoerd Rebers, Jordan Feld, Julie Bruneau, Marianne Martinello, Margaret Hellard, Gregory J Dore, Janke Schinkel, Marc van der Valk, Tanya Adams, Sophia Amjad, Christina Appelhans, Tanya Applegate, Brigitta Becker, Sanjay Bhagani, Rachel Bouchard, Dominique Braun, Christine Bruelisauer, Julie Bruneau, Selma Calcagnile, Anne Carroll, Orlando Cerocchi, Karen Chronister, Christiane Cordes, Greg Dore, Fiona Evans, Serge Fedele, Jordan Feld, Catherine Ferguson, Chris Fraser, Bruce Ganase, Ed Gane, Valerie George, Christoph Gerlach, Yvonne Gilleece, Rosie Gilliver, Jason Grebely, Christina Grube, Jenna Gustafson, Annette Haas, Michelle Hagenauer, Marianne Harris, Jeltje Helder, Margaret Hellard, Daniela Hirter, Mark Hull, Patrick Ingiliz, Stephanie Katz, Arthur Kim, Barbara Kotsoros, Melanie Lacalamita, Gabriella Lindergard, Thomas Lutz, Lester Macabodbod, Manuela Manz, Pip Marks, Marianne Martinello, Gail Matthews, Paola Messina, Karina Mohrmann, Christine Monnich, Juhi Moon, Alberto Moriggia, Genevieve Morris, Thomas Morrish, Mark Nelson, Victoria Oliver, Joanne Patterson, Martine Peters, Kathy Petoumenos, Hadassa Porretta, Andri Rauch, Parizade Raymode, Phillip Read, Stacey Reece, Jürgen Rockstroh, Angelika Saidi, Joe Sasadeusz, Pia Scherler, Reinhold Schröder, Marion Selfridge, Alison Sevehon, David Shaw, Mark Sulkowski, Mahshid Tamaddoni, Orla Thunder, Maria Christine Thurnheer, Elise Tu, Andrew Ustianowski, Marc van der Valk, Eric Witele
Journal: The Lancet Microbe (2023)

Microelimination of the hepatitis C virus (HCV) among men who have sex with men (MSM) could be complicated by continuous external introductions and the emergence of phylogenetic clusters harbouring clinically significant resistance-associated substitutions (RAS). To investigate international clustering and the prevalence and transmission of RAS, we aimed to analyse whole-genome HCV sequences from MSM with a recently acquired infection who participated in a large, international HCV treatment trial.For this whole-genome analysis, we obtained HCV sequences from 128 MSM who had acquired HCV within the past 12 months and were participating in the REACT trial. The participants from whom sequences were obtained were recruited at 24 sites in eight countries. We inferred maximum-likelihood phylogenies and identified transmission clusters for HCV genotypes separately. We constructed time-scaled phylogenies to estimate cluster introduction dates and used a Bayesian Skygrid approach to estimate the effective population size over the past 50 years. We calculated the prevalence of RAS and the extent of RAS transmission in the study population.The majority of recent HCV infections were part of international networks that arose in the late 1990s and early 2000s. Sequences obtained in the same country clustered frequently, and in 36% of subclusters since 2015 we found evidence of international transmission. European MSM were more likely than non-European MSM to be in a cluster (odds ratio 11·9 [95% CI 3·6-43·4], p<0·0001). The effective population size decreased rapidly since around 2015 in Europe. RAS associated with substantially diminished cure rates were infrequently detected and transmission of highly resistant viruses was not observed.Despite antiviral treatment becoming widely available, international transmission of HCV among MSM has still occurred over the past 8 years, which could complicate microelimination of the virus in this population. RAS-enriched clusters and widespread RAS transmission are currently not a threat to elimination goals. These findings support an international approach for HCV microelimination among MSM.National Institutes of Health and Dr. C.J. Vaillant Fonds.